rs11546512

Variant names:

• chr5-163513993-A-G
• rs11546512
• NM_013283.5:c.525A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_013283.5(MAT2B):​c.525A>G​(p.Leu175Leu) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,610,620 control chromosomes in the GnomAD database, including 16,808 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1375 hom., cov: 33)
  • Exomes 𝑓: 0.14 (15433 hom.)
• Consequence: MAT2B NM_013283.5 splice_region, synonymous
• Scores: Splicing: ADA: 0.1225
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 9 publications found

Genes affected

MAT2B (HGNC:6905): (methionine adenosyltransferase 2 non-catalytic beta subunit) The protein encoded by this gene belongs to the methionine adenosyltransferase (MAT) family. MAT catalyzes the biosynthesis of S-adenosylmethionine from methionine and ATP. This protein is the regulatory beta subunit of MAT. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAT2B	NM_013283.5	c.525A>G	p.Leu175Leu	splice_region_variant, synonymous_variant	Exon 4 of 7	ENST00000321757.11	NP_037415.1
MAT2B	NM_182796.2	c.492A>G	p.Leu164Leu	splice_region_variant, synonymous_variant	Exon 4 of 7		NP_877725.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAT2B	ENST00000321757.11	c.525A>G	p.Leu175Leu	splice_region_variant, synonymous_variant	Exon 4 of 7	1	NM_013283.5	ENSP00000325425.6

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18322 AN: 152134 Hom.: 1376 Cov.: 33

Gnomad AFR AF: 0.0575

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.127 AC: 31701 AN: 248896 AF XY: 0.133

Gnomad AFR exome AF: 0.0545

Gnomad AMR exome AF: 0.0647

Gnomad ASJ exome AF: 0.113

Gnomad EAS exome AF: 0.00745

Gnomad FIN exome AF: 0.218

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.141

GnomAD4 exome AF: 0.141 AC: 205337 AN: 1458368 Hom.: 15433 Cov.: 32 AF XY: 0.142 AC XY: 102808 AN XY: 725480

African (AFR) AF: 0.0538 AC: 1794 AN: 33340

American (AMR) AF: 0.0676 AC: 2984 AN: 44136

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 2871 AN: 26006

East Asian (EAS) AF: 0.0155 AC: 615 AN: 39552

South Asian (SAS) AF: 0.138 AC: 11819 AN: 85662

European-Finnish (FIN) AF: 0.214 AC: 11406 AN: 53296

Middle Eastern (MID) AF: 0.129 AC: 741 AN: 5746

European-Non Finnish (NFE) AF: 0.149 AC: 165191 AN: 1110378

Other (OTH) AF: 0.131 AC: 7916 AN: 60252

GnomAD4 genome AF: 0.120 AC: 18321 AN: 152252 Hom.: 1375 Cov.: 33 AF XY: 0.122 AC XY: 9111 AN XY: 74430

African (AFR) AF: 0.0573 AC: 2383 AN: 41576

American (AMR) AF: 0.101 AC: 1547 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3462

East Asian (EAS) AF: 0.0123 AC: 64 AN: 5194

South Asian (SAS) AF: 0.135 AC: 651 AN: 4830

European-Finnish (FIN) AF: 0.213 AC: 2250 AN: 10582

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10579 AN: 67994

Other (OTH) AF: 0.105 AC: 222 AN: 2112

Alfa AF: 0.137 Hom.: 2055

Bravo AF: 0.106

Asia WGS AF: 0.0920 AC: 322 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.78
PhyloP100		1.3
Mutation Taster		=63/37	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.12
dbscSNV1_RF	Benign	0.27
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11546512; hg19: chr5-162940999; COSMIC: COSV55200836; COSMIC: COSV55200836;